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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00383188




Registration number
NCT00383188
Ethics application status
Date submitted
28/09/2006
Date registered
2/10/2006

Titles & IDs
Public title
An Oral p38 Inhibitor Investigating Safety, Efficacy, And PK In Subjects With Active Rheumatoid Arthritis
Scientific title
A 12-WEEK, PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO INVESTIGATE THE SAFETY, PHARMACOKINETICS, AND EFFICACY OF PH 797804, ADMINISTERED ORALLY ONCE DAILY IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS
Secondary ID [1] 0 0
2006-003577-27
Secondary ID [2] 0 0
A6631007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthritis, Rheumatoid 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - placebo
Treatment: Drugs - PH-797804
Treatment: Drugs - PH-797804
Treatment: Drugs - PH-797804
Treatment: Drugs - PH-797804

Placebo comparator: 1 -

Experimental: 2 -

Experimental: 3 -

Experimental: 4 -

Experimental: 5 -


Treatment: Drugs: placebo
Capsule, once daily (QD) for 12 weeks

Treatment: Drugs: PH-797804
Capsule, 0.5 mg of PH-797804, once daily (QD) for 12 weeks

Treatment: Drugs: PH-797804
Capsule, 3 mg of PH-797804, once daily (QD) for 12 weeks

Treatment: Drugs: PH-797804
Capsule, 6 mg of PH-797804, once daily (QD) for 12 weeks

Treatment: Drugs: PH-797804
Capsule, 10 mg of PH-797804, once daily (QD) for 12 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) (ACR 20) Response at Week 12
Assessment method [1] 0 0
ACR20 responders: participants with greater than or equal to(\>=)20% improvement in tender and swollen 28-joint counts from baseline, \>=20% improvement in at least 3 of 5 measures: Patient's global assessment of arthritis(PGA), physician's global assessment of arthritis, participant's assessment of pain on visual analogue scale (Pain-VAS), health assessment questionnaire-disability index (HAQ-DI), C-reactive protein (CRP) in mg/liter (mg/L). PGA:participant assess overall disease activity on VAS, score:0(no arthritis) to 100(extreme arthritis), high score=more arthritis. Physician's global assessment:physician judge participant's overall disease activity on VAS, score:0(no arthritis) to 100millimeter(mm) (extreme arthritis), high score=more arthritis. Pain-VAS:participant assess arthritis pain on 100mm VAS, score:0mm (no pain) to 100mm (extreme pain), high score=more pain. HAQ-DI:functional disability evaluation, score:0 (no difficulty) to 3 (unable to do), high score=more disability.
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) (ACR 20) Response at Weeks 1, 2, 4, 8 and 16
Assessment method [1] 0 0
ACR20 responders: participants with greater than or equal to(\>=)20% improvement in tender and swollen 28-joint counts from baseline, \>=20% improvement in at least 3 of 5 measures: Patient's global assessment of arthritis(PGA), physician's global assessment of arthritis, participant's assessment of pain on visual analogue scale (Pain-VAS), health assessment questionnaire-disability index (HAQ-DI), C-reactive protein (CRP) in mg/L. PGA:participant assess overall disease activity on VAS, score:0(no arthritis) to 100(extreme arthritis), high score=more arthritis. Physician's global assessment:physician judge participant's overall disease activity on VAS, score:0(no arthritis) to 100millimeter(mm) (extreme arthritis), high score=more arthritis. Pain-VAS:participant assessed arthritis pain on 100mm VAS, score:0mm (no pain) to 100mm (extreme pain), high score=more pain. HAQ-DI:functional disability evaluation, score:0 (no difficulty) to 3 (unable to do), high score=more disability.
Timepoint [1] 0 0
Weeks 1, 2, 4, 8, 16
Secondary outcome [2] 0 0
Percentage of Participants Achieving American College of Rheumatology 50 Percent (%) (ACR 50) Response at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [2] 0 0
ACR50 responders: participants with \>= 50% improvement in tender and swollen 28-joint counts from baseline and \>= 50% improvement in at least 3 of the 5 measures: PGA, physician global assessment, Pain-VAS, HAQ-DI and C-reactive protein (in mg/L). PGA: participant assessed overall disease activity on VAS, score: 0 (no arthritis) to 100 (extreme arthritis), higher score=more arthritis. Physician global assessment: physician judged participant's overall disease activity on VAS, score: 0 (no arthritis) to 100 mm VAS (extreme arthritis), higher score=more arthritis. Pain-VAS: participant assessed arthritis pain by 100 mm VAS, score: 0 mm (no pain) to 100 mm (extreme pain), higher score=more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.
Timepoint [2] 0 0
Weeks 1, 2, 4, 8, 12 and 16
Secondary outcome [3] 0 0
Percentage of Participants Achieving American College of Rheumatology 70 Percent (%) (ACR 70) Response at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [3] 0 0
ACR70 responders: participants with \>=70% improvement in tender and swollen 28-joint counts from baseline and \>= 70% improvement in at least 3 of the 5 measures: PGA, physician global assessment, Pain-VAS, HAQ-DI and CRP (in mg/L). PGA: participant assessed overall disease activity on VAS, score: 0 (no arthritis) to 100 (extreme arthritis), higher score=more arthritis. Physician global assessment: physician judged participant's overall disease activity on VAS, score: 0 (no arthritis) to 100 mm VAS (extreme arthritis), higher score=more arthritis. Pain-VAS: participant assessed arthritis pain by 100 mm VAS, score: 0 mm (no pain) to 100 mm (extreme pain), higher score=more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.
Timepoint [3] 0 0
Weeks 1, 2, 4, 8, 12 and 16
Secondary outcome [4] 0 0
Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [4] 0 0
A total of 28 tender/painful joints were assessed for tenderness or pain. The 28 joints included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees. Artificial joints were not assessed.
Timepoint [4] 0 0
Baseline, Weeks 1, 2, 4, 8, 12 and 16
Secondary outcome [5] 0 0
Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [5] 0 0
A total of 28 swollen joints were assessed. The 28 joints included: shoulders, elbows, wrists, MCP joints, PIP joints, and knees. Artificial joints were not assessed.
Timepoint [5] 0 0
Baseline, Weeks 1, 2, 4, 8, 12 and 16
Secondary outcome [6] 0 0
Change From Baseline in Participant Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [6] 0 0
Participants self-assessed the severity of arthritis pain using a 100 mm VAS between 0 mm (no pain) and 100 mm (most severe pain), where higher scores indicate higher degree of pain intensity.
Timepoint [6] 0 0
Baseline, Weeks 1, 2, 4, 8, 12 and 16
Secondary outcome [7] 0 0
Change From Baseline in Participant Global Assessment (PGA) of Arthritis at Weeks 1, 2, 4, 8 12 and 16
Assessment method [7] 0 0
Participants responded to the question "Considering all the ways your arthritis affects you, how are you feeling today?" was recorded using a 0-100 mm VAS where 0 mm (very well) and 100 mm (very poor). Higher scores indicated worse condition.
Timepoint [7] 0 0
Baseline, Week 1, 2, 4, 8, 12 and 16
Secondary outcome [8] 0 0
Change From Baseline in Physician Global Assessment of Arthritis at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [8] 0 0
Physician assessed the overall impact of arthritis on the participants' daily life based on the disease signs, functional capacity and physical examination. The physician's response was recorded using a 100 mm VAS between 0 mm (very good) and 100 mm (very poor). Higher scores indicating worse condition of arthritis.
Timepoint [8] 0 0
Baseline, Week 1, 2, 4, 8, 12 and 16
Secondary outcome [9] 0 0
Change From Baseline in C-Reactive Protein (CRP) at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [9] 0 0
C-reactive protein is a biochemical measure of inflammation and disease activity.
Timepoint [9] 0 0
Baseline, Week 1, 2, 4, 8, 12 and 16
Secondary outcome [10] 0 0
Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4 [CRP]) at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [10] 0 0
DAS28-4 (CRP) was calculated from 28-tender joint count and 28-swollen joint count, C-reactive protein (mg/L) and PGA : participant assessed overall disease activity on VAS, score:0(no arthritis) to 100(extreme arthritis). DAS28-4 (CRP) lower than (\<) 3.2 implied mild disease activity, 3.2 to 5.1 implied moderate disease activity and greater than (\>) 5.1 severe disease activity. Total score range: 0 to 9.4, higher score indicated more disease activity.
Timepoint [10] 0 0
Baseline, Weeks 1, 2, 4, 8, 12 and 16
Secondary outcome [11] 0 0
Number of Participants Who Withdrew From Study Due to Lack of Efficacy
Assessment method [11] 0 0
Timepoint [11] 0 0
Baseline up to Week 16
Secondary outcome [12] 0 0
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 1, 2, 4, 8, 12 and 16
Assessment method [12] 0 0
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dressing/grooming, arising, eating, walking, reaching, gripping, hygiene, and "other common activities" over past week. Each item scored on 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total average possible score range 0 (least difficulty) to 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.
Timepoint [12] 0 0
Baseline, Week 1, 2, 4, 8, 12 and 16
Secondary outcome [13] 0 0
Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-SF) Score at Weeks 1, 2, 4, 8 and 12
Assessment method [13] 0 0
The modified brief pain inventory-short form (mBPI-SF) is a pain assessment tool used to measure both pain intensity and pain interference using an 11-point numeric rating scale. Participants rated their pain severity, using a scale from 0 (no pain) to 10 (pain as bad as you can imagine), where higher scores indicate greater intensity of pain. Participants also rated the level of pain interference using a scale from 0 (no interference) to 10 (complete interference), where higher scores indicate more degree of interference in general daily activities.
Timepoint [13] 0 0
Baseline, Week 1, 2, 4, 8 and 12
Secondary outcome [14] 0 0
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2 at Weeks 4 and 12
Assessment method [14] 0 0
The SF-36 version 2 is a 36-item generic health status measure standardized survey is a standardized survey evaluating 8 domains of functional health and well-being: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE) and mental health (MH). The summary score of these concepts is summarized as Physical component summary (PCS) score and Mental component summary (MCS) score, are based on a normalized sum of the 8 scale scores PF, RP, BP, GH, VT, SF, RE, and MH. The score for each of 8 domains were scaled from 0 (lowest level of functioning) to100 (highest level of functioning, where higher scores represented better level of functioning. 8 domains were summarized as 2 summary scores; PCS and MCS. Score range for each of the 2 summary scores = 0 (lowest level of functioning) to 100 (highest level of functioning), where higher scores represented better level of functioning.
Timepoint [14] 0 0
Baseline, Weeks 4, 12
Secondary outcome [15] 0 0
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Assessment method [15] 0 0
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events are events between first dose of study drug and up to week 16 after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.
Timepoint [15] 0 0
Baseline up to Week 16
Secondary outcome [16] 0 0
Number of Participants With Laboratory Abnormalities
Assessment method [16] 0 0
Haemoglobin, haematocrit, red blood cell count less than(\<) 0.8\*lower limit of normal \[LLN\], platelets \<0.5\*LLN and (\&) greater than(\>) 1.75\*ULN, white blood cell count \<0.6\*LLN\&\>1.5x ULN, lymphocytes \<0.8\*LLN\&\>1.2\*ULN, total neutrophils \<0.8\*LLN\&\>1.2\*ULN, basophils, eosinophils, monocytes \>1.2\*ULN; total bilirubin \>1.5\*ULN, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase \>3.0\*ULN, total protein \<0.8\*LLN\&\>1.2\*ULN, albumin \<0.8\*LLN\&\>1.2\*ULN; blood urea nitrogen, Creatinine, Uric Acid \>1.2\*ULN; Cholesterol \>1.3\*ULN, HDL Cholesterol \<0.8\*LLN, LDL Cholesterol \>1.2\*ULN, Triglycerides \>1.3\*ULN; Electrolytes: sodium \<0.95\*LLN\&\>1.05\*ULN, potassium \<0.9\*LLN\&\>1.1\*ULN, chloride, calcium, magnesium, bicarbonate \<0.9\*LLN\&\>1.1\*ULN, phosphate \<0.8\*LLN\&\>1.2x ULN; glucose \<0.6\*LLN\&\>1.5\*ULN, human chorionic gonadotrophin \>0; CRP \>1.25\*ULN, (\[urine-RBC, WBC, epithelial cells, crystals, yeast cells\] \>=6), urine casts \>1, urine Bacteria \>20.
Timepoint [16] 0 0
Baseline up to Week 16
Secondary outcome [17] 0 0
Number of Participants With Clinically Significant Vital Signs Abnormalities
Assessment method [17] 0 0
Pre-defined criteria for vital sign abnormalities: Maximum (max) increase from baseline in supine systolic blood pressure (SBP) \>=30 milliliters of mercury (mmHg), maximum increase from baseline in supine diastolic blood pressure (DBP) \>=20 mmHg.
Timepoint [17] 0 0
Baseline up to Week 16
Secondary outcome [18] 0 0
Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Parameters
Assessment method [18] 0 0
12-lead ECG were performed after the participant had rested quietly for at least 10 minutes in a supine position. ECG parameters included RR interval, PR interval, QRS complex, QT interval, corrected QT (QTc) interval, Bazett's correction QT (QTcB) interval, Heart Rate and Fridericia's correction (QTcF) interval. Clinical significance of 12-Lead ECG was judged by investigator.
Timepoint [18] 0 0
Baseline up to Week 16
Secondary outcome [19] 0 0
Number of Participants With Electrocardiogram (ECG) Abnormalities
Assessment method [19] 0 0
Criteria for ECG abnormalities: maximum QT interval (millisecond \[msec\]): \< 450, 450 to \<480, 480 to \<500, \>= 500; maximum QT interval with Bazett's correction (QTcB interval) (msec): \<450, 450 to \<480, 480 to \<500, \>=500; maximum QT interval with Fridericia's correction (QTcF interval) (msec): \<450, 450 to \<480, 480 to \<500, \>=500; maximum QTc interval increase from baseline (msec): change \<30, 30 \<=change \<60, change \>=60.
Timepoint [19] 0 0
Baseline up to Week 16
Secondary outcome [20] 0 0
Number of Participants With Clinically Significant Physical Examination Abnormalities
Assessment method [20] 0 0
Following criteria and body systems were examined to identify the clinically significant physical examination abnormalities; general appearance, skin (presence of rash), head, ears, eyes, nose, and throat, lungs (auscultation), heart (auscultation for presence of murmurs, gallops, rubs, peripheral edema), abdominal (palpation and auscultation), neurologic (mental status, station, gait, reflexes, motor and sensory function, coordination). Physical examination abnormalities were as determined by the investigator.
Timepoint [20] 0 0
Baseline up to Week 16
Secondary outcome [21] 0 0
Minimum Observed Plasma Pre-dose Concentration (Ctrough Min) of Steady State
Assessment method [21] 0 0
Timepoint [21] 0 0
Predose
Secondary outcome [22] 0 0
Number of Participants With Concomitant Medications
Assessment method [22] 0 0
Concomitant medication (any medication other than, and in addition to, the study medication) taken for any period of time during the study and was coded by World Health Organization (WHO) medical dictionary.
Timepoint [22] 0 0
Baseline up to Week 16

Eligibility
Key inclusion criteria
* Diagnosed with RA and has failed at least 1 DMARD therapy
Minimum age
19 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any other inflammatory arthritis and any significant history of acute or chronic infection with immunomodulatory etiology.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/12/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/07/2008
Sample size
Target
Accrual to date
Final
305
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Emeritus Research - Malvern East
Recruitment postcode(s) [1] 0 0
3145 - Malvern East
Recruitment outside Australia
Country [1] 0 0
Brazil
State/province [1] 0 0
Paraná
Country [2] 0 0
Brazil
State/province [2] 0 0
PR
Country [3] 0 0
Brazil
State/province [3] 0 0
SP
Country [4] 0 0
Chile
State/province [4] 0 0
RM
Country [5] 0 0
Chile
State/province [5] 0 0
V Region
Country [6] 0 0
Chile
State/province [6] 0 0
VI Región
Country [7] 0 0
Czechia
State/province [7] 0 0
Brno
Country [8] 0 0
Czechia
State/province [8] 0 0
Olomouc
Country [9] 0 0
Czechia
State/province [9] 0 0
Ostrava - Trebovice
Country [10] 0 0
Czechia
State/province [10] 0 0
Praha 2
Country [11] 0 0
Czechia
State/province [11] 0 0
Praha 4
Country [12] 0 0
Czechia
State/province [12] 0 0
Zlin
Country [13] 0 0
Estonia
State/province [13] 0 0
Tallinn
Country [14] 0 0
India
State/province [14] 0 0
Andhra Pradesh
Country [15] 0 0
India
State/province [15] 0 0
Karnataka
Country [16] 0 0
India
State/province [16] 0 0
Maharashtra
Country [17] 0 0
India
State/province [17] 0 0
Punjab
Country [18] 0 0
India
State/province [18] 0 0
Tamil NADU
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Anyang
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Peru
State/province [21] 0 0
Lima
Country [22] 0 0
Poland
State/province [22] 0 0
Bialystok
Country [23] 0 0
Poland
State/province [23] 0 0
Poznan
Country [24] 0 0
Poland
State/province [24] 0 0
Warszawa
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Moscow
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Smolensk
Country [27] 0 0
Russian Federation
State/province [27] 0 0
St. Petersburg
Country [28] 0 0
South Africa
State/province [28] 0 0
Gauteng
Country [29] 0 0
South Africa
State/province [29] 0 0
Johannesburg
Country [30] 0 0
South Africa
State/province [30] 0 0
Bloemfontein
Country [31] 0 0
South Africa
State/province [31] 0 0
Durban
Country [32] 0 0
South Africa
State/province [32] 0 0
Kempton Park
Country [33] 0 0
South Africa
State/province [33] 0 0
Pretoria
Country [34] 0 0
Spain
State/province [34] 0 0
Vizcaya
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT00383188